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HIV Resistance
In the last 3 decades, HIV has risen in prevalence to become an international pandemic of epic proportions. HIV, or Human Immunodeficiency Virus, is a zoonotic retrovirus that compromises and eventually obliterates its host's immune system through the systemic destruction of T-Helper (CD4) cells and later macrophages and dendritic cells as the disease progresses. HIV is spread through bodily fluid contact, the most prominent type of spread being through heterosexual sexual contact. HIV is said to have progressed to AIDS or Acquired Immunodeficiency Syndrome, once an individuals CD4 serum (blood) concentration drops to 200 cells per micro-liter. Once this has occurred, a person's CD4 count rapidly declines and they become susceptible to myriad of pathogens and malignancies not commonly seen within human populations, even within immunocommpromised populations. The individual eventually succumbs to a secondary opportunistic infection. The most recent data suggests that there are currently more than 40 million people living with HIV today. But there is a small percentage of individuals, mostly of European descent, who are resistant to HIV-1 due to a CCR5 gene mutation. Delta32 CCR5 The CCR5 gene on the short (p) arm of the third chromosome at position 21 encodes the amino acid sequence and thus the protein structure of CC chemokine receptor 5, an integral membrane found on the cell membrane of a select group of white blood cells that includes T-lymphocytes, macrophages and dendritic cells (1). Though HIV actually binds to the CD4 glycoprotein expressed by T-lymphocytes, macrophages and dentritic cells, many strains of HIV-1 require the presence of a functional CCR5 protein to properly bind to a susceptible cell. Those with a Delta32 CCR5 gene mutation will express severely shortened CCR5 proteins that cannot be properly inserted into plasma membrane and are thus non-functional and eventually degraded by the cell (1,2). The absence of this integral protein inhibits HIV-1 viral entry, preventing the development of HIV and thus AIDS. The Delta32 CCR5 haploid is inherited in simple autosomal recessive manner (1). This means that those who are heterozygous for the Delta32 CCR5 gene mutation will have typical susceptibility to HIV. Those who are homologous for the Delta32 CCR5 mutation are afforded any resistance to most strains of HIV-1, though they remain susceptible to HIV-2 and all strains of HIV-1 that (like HIV-2) use the chemokine receptor CXCR4 for entry(1,2). History and Prevalence The Delta32 CCR5 gene mutation appears to be more prevalent among those of European descent. Early genetic evidence suggested that this beneficial mutation arose and gained prevalence in the last 1,000 years of human history, leading many researchers to believe that the Delta32 CCR5 mutation gained prominence because it offered resistance against one of the many great pestilences to sweep Europe in the last millennium. Many experts thus speculated that the Delta32 CCR5 mutation gained prevalence due to the selective pressure of either the Bubonic plague or smallpox. More recent research however suggests that this mutation arose much earlier in human history, possibly up to 5,000 years ago, and that it was just as prevalent within European populations 3,000 years ago as it is today. This knowledge discredits any previous claims that the prevalence of the Delta32 CCR5 mutation within European populations is somehow related to the many smallpox or bubonic plagues epidemics to decimate Europe in medieval times. Researchers are currently divided as to how the Delta32 mutation penetrated in the European haplotype; some believe that the mutation offered some sort of survival advantage in prehistoric times while others postulate that its prevalence is merely a happy coincidence(2). Kara Proctor's Genotype After analyzing her genome, 23andMe has concluded that Kara Proctor, like 10-14% of all those with European ancestry, is heterozygous for the Delta32 CCR5 mutation at gene marker i3003626 on chromosome 3. Though Proctor is not resistant to HIV infection, several studies have suggested that Delta32 CCR5 heterozygotes experience slower HIV progression. It should be noted however that HIV progression is depends upon plethora of environmental, genetic and epigenetic factors and cannot be predicted solely by examining one chromosomal locus. When 23andMe analyzed Proctor's genotype at the rs2395029 marker on chromosome 6, another marker used to assess one's HIV progression, it was speculated that she (based on this marker) would experience normal HIV progression if she were ever to contract the retrovirus(2). References 1. CCR5 Wikipedia Article 2. 23andMe